PROJECT SUMMARY Precision medicine individualizes disease treatment and prevention strategies for each person. Molecular imaging (MI) plays a key role in precision medicine because it visualizes the biological processes underlying the development of disease that are unique to each individual. MI requires an imaging probe that targets processes like angiogenesis and inflammation and reports the location of the activity inside the body. Current preclinical (ultrasound) and clinical (positron emission tomography) MI applications have the drawbacks of limited body coverage and poor spatial resolution, respectively. Computed tomography (CT) produces high-resolution 3- dimensional whole body images but has fallen behind other MI modalities because it lacks a clinically viable targeted imaging probe. The long-term goal of this research is to adapt and enhance an existing, readily available imaging modality, CT, for clinical molecular imaging by introducing an imaging probe that targets disease and is detectable by x-ray. The specific aims of this project are 2-fold. The first aim is to develop a novel CT molecular imaging agent by combining the established platform of targeted microbubble contrast agents used in ultrasound with radiopaque polyesters synthesized with a unique, aliphatic, iodinated monomer detectable by CT to produce targeted iodinated microbubble (TIMb). The radio-contrast properties of TIMbs will be evaluated versus iodine loading, temperature and concentration. The second aim is to test TIMb and CT parameters in an in vivo model of angiogenesis and compare sensitivity to ultrasound MI. The outcome of this project will be TIMb, a targeted contrast agent for CT, which can be used as a tool for early detection, fundamentally improving the treatment and prevention of disease. This is the first step toward establishing CT as a clinically viable option for molecular imaging to facilitate high-resolution whole body molecular imaging needed in the push toward precision medicine.